The present invention relates to a specialized method and to disposable units for the circulation of fluids for perfusion-induced hyperthermia, including extracorporeal blood heating and sorbent-based detoxification, as an antiviral and antineoplasm protocol.
Hyperthermia as a treatment of tumors has been carefully studied and applied since the 1960s. Prior to that time there were multiple reports of tumor regression coincident with febrile episodes. Subsequent analysis revealed that temperatures greater than 41xc2x0 C. are ordinarily needed to induce tumor necrosis (tumor death). Although there are multiple methods of inducing hyperthermia by either direct skin contact or radiant heating, many physicians now favor an extracorporeal heat exchange (blood) circuit to raise patient temperatures. Others favor heating body cavities, such as the peritoneal cavity, with heated fluids to create hyperthermia of the tissue surfaces within the cavity. Patients may be maintained at 41.5xc2x0 to 42xc2x0 C. (rectal a) temperature) for three to four hours without severe cardiovascular compromise, although others report elevation of serum transaminases and bilirubin in patients kept at these temperatures for greater than 10 to 40 minutes. Instances of neurologic damage have been reported in association with serum hypophosphatemia, although no significant problems occurred once phosphate levels were maintained. Deaths have also been reported in two patients receiving hyperthermia at 41.5xc2x0 to 42xc2x0 C. for 1-xc2xd to 2hours, presumably from massive liver tumor necrosis.
DeMoss, J. L. et al., xe2x80x9cHyperthermia in the Treatment of Cancer,xe2x80x9d The Journal of Extra-Corporeal Technology, Volume 17,No. 1, pp. 37-43, 1985, explains that tumors are vulnerable to heat and that the goal of hyperthermiic treatment therapy is to achieve cytotoxic temperatures in the tumor for a sufficient length of time without damaging the surrounding normal tissue. The rate at which blood flows through any given area of tissue determines the amount of heat that may be carried away and therefore is a major determinant of the temperature rise in that tissue. In normal tissue, heat causes vasodilation. In a tumor, the microvasculature is made up of an overabundance of capillary beds which are unable to dilate. Blood flow through the area is thus more sluggish and commensurately unable to dissipate heat applied to the area. The inability to respond to heat by dilation, as normal vasculature would, also subjects the tumor to hypoxia, anaerobic metabolism and local acidosis, and these conditions in turn make the tumor tissue more vulnerable to thermal injury.
Other literature addressing the utility of hyperthermia in the treatment of malignancy includes: Sanchez, R., xe2x80x9cOverview of Whole Body Hyperthermia Experience at American International Hospital,xe2x80x9d Consensus on Hyperthermia for the 1990s, Plenum Press, New York, pp. 203-208 (1990); Levin, R. D. et al., xe2x80x9cWhole Body Hyperthermia Experience in Breast Cancer at American International Hospital,xe2x80x9d Consensus on Hyperthermia for the 1990s Plenum Press, New York, pp.387-391 (1990); Perez, C. A. et al., xe2x80x9cRandomized Phase III Study Comparing Irradiation and Hyperthermia with Irradiation Alone in Superficial Measurable Tumors,xe2x80x9d Am. J. Clin. Oncol. Vol. 14, No. 2, pp. 133-141 (1991); and others.
Patents relating to methods for the extracorporeal treatment of blood for cancers, viruses and parasites include U.S. Pat. No. 2,886,771 to Vincent, No. 3,482,575 to Claff, No.4,061,141 to Hyden, No.4,191,182 to Popovich, No.4,321,918 to Clark, No. 4,322,275 to Jain, No. 4,381,004 to Babb, No. 4,479,798 to Parks, No. 4,540,401 to Marten, No.4,563,170 to Aigner, No.4,576,143 to Clark and No.4,692,188 to Troutner et al.
There were two reasons for exploring the use of hyperthermia as a treatment for viral-associated neoplasms when such work began a few years ago. First, hyperthermia was known to have caused tumor regression in both animal and in human sarcomas. Studies on the biochemical and physiologic effects of hyperthermia had shown that damage to microvasculature is important for tissue necrosis associated with heat Second, the human lymphadenopathy associated virus was known to be heat-sensitive. McDougal et al. incubated lymphadenopathy associated virus at temperatures ranging from 37xc2x0 to 60xc2x0 C. and found the log kill followed first order kinetics. Thermal inactivation was decreased when the virus was in the lyophilized state compared to the liquid state (10-fold loss in LD50 121 seconds at 56xc2x0 C. for virus in media versus 32 minutes in lyophilized state). It was also found that lymphadenopathy virus was 40% inactivated after 30 minutes in a 42xc2x0 water bath, and 100% inactivated after the same time period at 56xc2x0 C. Thus, hyperthermia can benefit patients suffering from viral infections in two ways. First, the hyperthermia kills malignant cells in the viral-associated neoplasms. Second, the hyperthermia directly inactivates the viruses themselves by denaturing them.
Studies have previously been completed in which whole body hyperthermia, achieved via extracorporeal circulation and thermoregulation, was used to treat Kaposi""s Sarcoma associated with human immunodeficiency virus infection. While evaluation of the therapeutic effects of such treatment was the primary purpose of these studies, the simultaneous effects on HIV (human immunodeficiency virus) disease were evaluated by studying immunologic and virologic parameters of HIV infection as well as immunologic parameters related to Kaposi""s Sarcoma In fact, the use of hyperthennia in AIDS (acquired inmmunodeficiency syndrome) patients with Kaposi""s Sarcoma has received considerable public and media attention. The first two patients upon whom this procedure was performed were patients of the Atlanta pathologist Dr. Kenneth Alonso. Dr. Alonso initiated this experimental use of hyperthernia with Dr. William Logan, Jr., an Atlanta surgeon, as a pilot project to examine the possible use of this technique in the treatment of HIV associated diseases. Subsequently, Dr. Alonso requested that the National Institute of Allergy and Infectious Fri Diseases (NLAID) evaluate the study techniques, results and patients.
As reported in O""Malley, S., xe2x80x9cHyperthernia: Perfusion""s Answer . . . ?xe2x80x9d, Perfusion Life, January 1991, pp. 6-13, a patient named Carl Crawford experienced a dramatic recovery from head-to-toe skin cancers after being treated with extracorporeal blood heating. (This case study was published in Logan, W. D. et al., xe2x80x9cCase Report: Total Body Hyperthermia in the Treatment of Kaposi""s Sarcoma.,xe2x80x9d Med. Oncol. and Tumor Pharmacother. Vol. 8, No. 1, pp. 45-47 (1991).) Mr. Crawford had been diagnosed as having Kaposi""s Sarcoma incident to human immunodeficiency virus infection, and had been told he had only 2 to 4 weeks left to live. Mr. Crawford was the first patient of Drs. Alonso and Logan, who together with perfasionist Joseph A. Guzman heated his blood to 42xc2x0 C. which, the doctors said, killed the human immunodeficiency virus. Although NIAID discounted Mr. Crawford""s recovery due to an alleged error in diagnosisxe2x80x94NLAMD maintained that Mr. Crawford never had Kaposi""s Sarcoma but had cat-scratch fever insteadxe2x80x94six other doctors besides Drs. Alonso and Logan had diagnosed Mr. Crawford""s skin lesions as Kaposi""s Sarcoma and growing numbers of physicians are convinced that hyperthermia provides a proven antiviral protocol. For example, Dr. Robert S. Jenkins, Medical Director of the Immuno Suppressed Unit at Hollywood Community Hospital, believes that the hyperthermia was responsible for curing Mr. Crawford""s Kaposi""s Sarcoma lesions.
In a completely separate effort from Drs. Alonso and Logan, Dr. Shawn Hankins, a chiropractor in Port Angeles, Wash., has supported hyperthermia treatments since July 1987 (as explained in the Acquired Immunodeficiency Syndrome Treatment News, Issue No. 104, Jun. 1, 1990, p. 2). He points out that human immunodeficiency virus is heat sensitive and, in addition, hyperthermia can cause increased T-cell proliferation, phagocytosis, and increased production of antibodies and interferon. Observations of patient improvement which sometimes follows pneumocystitis (which causes a high fever) also support this conclusion.
Other publications directed generally toward the treating of human inmmunodeficiency virus with heat include: Weatherburn, H., xe2x80x9cHyperthermia . . .,xe2x80x9d The British Journal of Radiolog Vol. 61, No. 729, pp. 863-864 (1988); Yatvin, M. B., xe2x80x9cAn Approach. Using Hyperthermia and Membrane Modification,xe2x80x9d Medical Hvpotheses, Vol. 27, pp. 163-165 (1988); and U.S. Pat. No. 4,950,225 to Davidner et al., xe2x80x9cMethod for Extracorporeal Blood Shear Treatment.xe2x80x9d
The latter, Davidner et al., discusses the extracorporeal treatment of the blood of a human immunodeficiency virus patient with a) hyperthermia; b) mechanical shear and/or c) irradiation. When hyperthermia is used, the blood is heated to between 41.00 and 42.5xc2x0 C. (or somewhat higher), and pH is adjusted by oxygenating the blood with an extracorporeal oxygenator and by adding sodium bicarbonate intravenously when necessary. Blood is held under low flow or static conditions, extracorporeally, so that the blood treatment or treatments are (assertedly) maximally successful in ineffectuating the human irumunodeficiency virus.
U.S. Pats. No. 5,354,277 and No.5,476,444 are directed to methods and apparatus for effecting whole-body hyperthermia, but even these designs may be improved by incorporating fluid handling systems in which the temperature of the fluid can be controlled more easily, in which the risk of contamination is minimized, and in which the design of the fluid handling system is optimized for a particular indication. A need therefore exists for disposable fluid handling systems with specialized configurations.
The present invention is a method and device for extracorporeal treatment of a patient by heating the patient""s blood and/or a regional anatomic area which utilizes an optional hemodialysis machine capable of heating the fluids to 48xc2x0 C., an optional parallel plate dialyzer together with a sorbent-based detoxifier, a tubular heat exchanger and a high flow positive displacement pump-in addition to various probes and catheters. The present invention is further a method and device for circulating heated perfusion fluid within a body cavity of a patient utilizing a heat exchanger, heater and high flow positive displacement pump in addition to various catheters, fluid sets and sensors. The present invention also includes a disposable tubing set for directing fluids used in extracorporeal hyperthermia procedures. The tubing set contains a fluid reservoir, accommodates the positive displacement pump, and includes a heat exchanger for heating blood or fluid. The specific improvements in extracorporeal heating afforded by this w system inhere in the combined high flow of the pump and the high temperature-up to 52xc2x0 C.xe2x80x94achievable in the heat exchanger to achieve fast heating of the perfusion fluid to a temperature sufficient so that at the time such fluid enters the body cavity of the patient the perfusion fluid is at least 41xc2x0 C. up to 48xc2x0 C., and preferably about 430xc2x0 C. to 45xc2x0 C., which together provide unprecedented speed and efficiency in the administration of hyperthermia treatments in extracorporeal blood or circuits. Computer controlled alarms provide enhanced safety monitoring. The prepackaged blood or sterilized fluid handling system enhances safety and may be configured to respond to a particular indication.